Sequential Palladium‐Catalysed Direct Arylation Followed by Suzuki Coupling of Bromo‐2‐chloropyridines: Simple Access to a Variety of 2‐Arylpyridines

Abstract

Abstract2‐Arylpyridines are an important class of ligands for the synthesis of complexes with physical properties. We observed that the use of 3‐, 4‐ or 5‐bromo‐2‐chloropyridines allows the synthesis of a wide variety of heteroarylated 2‐arylpyridines by means of successive direct arylation and Suzuki coupling. For these two reactions, an air‐stable catalyst associated to a cheap and nontoxic base was employed as the catalyst. Moreover, a wide range of heteroarenes and functionalised arylboronic acids could be tolerated.

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

“…Doucet and co-workers also investigated the PdA C H T U N G T R E N N U N G (OAc) 2 /dppb-catalyzed arylation of 2-substituted furans with equimolar amounts of commercially available bromo-2-chloropyridines and found that 5-aryl derivatives of general formula 58 were obtained in good yields using, also in this case, KOAc as the base and DMA as the solvent (Scheme 22). [32] A quite low yield was, however, obtained in the PdA C H T U N G T R E N N U N G (OAc) 2 /dppb-catalyzed C-3 arylation of 2-ethylbenzo[b]furan (59) with 4-bromo-2-chloropyridine (Scheme 23). [32] It was then observed that the heteroarylated 2-chloropyridines resulting from the chemoselective C-5 arylation of 2-substituted five-membered heteroarenes bearing one or two heteroatoms with 4-bromo-2-chloropyridine were able to undergo PdA C H T U N G T R E N N U N G (OAc) 2 /dppbcatalyzed Suzuki-type reactions with arylboronic acids to give 2-arylpyridine derivatives in high yields.…”

“…[32] A quite low yield was, however, obtained in the PdA C H T U N G T R E N N U N G (OAc) 2 /dppb-catalyzed C-3 arylation of 2-ethylbenzo[b]furan (59) with 4-bromo-2-chloropyridine (Scheme 23). [32] It was then observed that the heteroarylated 2-chloropyridines resulting from the chemoselective C-5 arylation of 2-substituted five-membered heteroarenes bearing one or two heteroatoms with 4-bromo-2-chloropyridine were able to undergo PdA C H T U N G T R E N N U N G (OAc) 2 /dppbcatalyzed Suzuki-type reactions with arylboronic acids to give 2-arylpyridine derivatives in high yields. [32] The synthesis of 1-[5-(2-phenylpyridin-3-yl)furan-2-yl]-butan-1-one (60) from compound 58d and phenylboronic acid is illustrated in Scheme 24.…”

“…[32] It was then observed that the heteroarylated 2-chloropyridines resulting from the chemoselective C-5 arylation of 2-substituted five-membered heteroarenes bearing one or two heteroatoms with 4-bromo-2-chloropyridine were able to undergo PdA C H T U N G T R E N N U N G (OAc) 2 /dppbcatalyzed Suzuki-type reactions with arylboronic acids to give 2-arylpyridine derivatives in high yields. [32] The synthesis of 1-[5-(2-phenylpyridin-3-yl)furan-2-yl]-butan-1-one (60) from compound 58d and phenylboronic acid is illustrated in Scheme 24. [32] Recently, Bruneau and co-workers reported that 4-(furan-2-ylmethyl)-2-phenethyl-1,2,3,4-tetrahydroisoquinoline (61) underwent selective arylation at position 5 of the furan ring by treatment with 1-bromonaphthalene and aryl bromides bearing an electronwithdrawing group in DMA at 150 8C in the presence of KOAc as the base and a catalytic amount of PdA C H T U N G T R E N N U N G (OAc) 2 (Scheme 25).…”

“…[32] The synthesis of 1-[5-(2-phenylpyridin-3-yl)furan-2-yl]-butan-1-one (60) from compound 58d and phenylboronic acid is illustrated in Scheme 24. [32] Recently, Bruneau and co-workers reported that 4-(furan-2-ylmethyl)-2-phenethyl-1,2,3,4-tetrahydroisoquinoline (61) underwent selective arylation at position 5 of the furan ring by treatment with 1-bromonaphthalene and aryl bromides bearing an electronwithdrawing group in DMA at 150 8C in the presence of KOAc as the base and a catalytic amount of PdA C H T U N G T R E N N U N G (OAc) 2 (Scheme 25).…”

Nachrichten des Verbandes Biologie, Biowissenschaften & Biomedizin in Deutschland

“…Doucet and co‐workers also investigated the Pd(OAc) 2 /dppb‐catalyzed arylation of 2‐substituted furans with equimolar amounts of commercially available bromo‐2‐chloropyridines and found that 5‐aryl derivatives of general formula 58 were obtained in good yields using, also in this case, KOAc as the base and DMA as the solvent (Scheme ) 32…”